Morbidity and mortality among children, adolescents, and young adults with cancer over six decades: a Swedish population-based cohort study (the Rebuc study)

Summary Background Despite progress in managing cancer in children, adolescents, and young adults (CAYAs), persistent complications may impact their quality of life. This study covers the morbidity and mortality, among CAYAs, with the aim to investigate the influence of socioeconomic factors on outcomes. Methods This retrospective matched cohort study included the entire Swedish population of individuals under 25 with cancer 1958–2021. The population was identified from the Cancer Register, and controls were paired 1:5 based on age, sex, and residence. Multiple registers provided data on morbidity, mortality, and demographics. Findings This survey covering 63 years, identified 65,173 CAYAs and matched controls, a total of 378,108 individuals (74% females). CAYAs exhibited a 3.04-times higher risk for subsequent cancer (Odds ratio (OR) 95% confidence interval (CI) 2.92–3.17, p < 0.0001), a 1.23-times higher risk for cardiovascular disease (OR 95% CI 1.20–1.26, p < 0.0001), and a 1.41-times higher risk for external affliction (OR 95% CI 1.34–1.49, p < 0.0001). CAYAs had a higher mortality hazard, and after adjusting for socioeconomic factors, males, individuals born outside Europe, and those with greater sick-leave had a higher association with mortality, while education and marriage showed a beneficial association. Interpretation The Rebuc study, showed an increased risk for serious complications among young cancer patients in Sweden. Patient-specific variables, demographics, and socioeconomic factors influenced mortality. These results underscore the impact of cancer on the health and lifespan of young individuals and the necessity for further research to address socioeconomic disparities in cancer care. Funding Grants from the 10.13039/100010805Medical Research Council of Southeast Sweden (FORSS), ALF Grants, Region Ostergotland, and The Swedish Childhood Cancer Fund.


Supplementary appendix
Page Municipalities and healthcare regions in Sweden 1 Supplementary Figures Figure 1.Flowchart of the study population.
2 Figure 2. National registers over time 2 Figure 3. Cumulative mortality for 12 index diagnoses 7 Figure 4. All-cause mortality in males and females and in the three age groups 8 Supplementary Tables Tabel 1.The National Board of Health and Welfare's Registers 3 Table 2. ICD 10 codes and the translation process from ICD 7-9. 4 Tabel 3. Time, age, sex, and socioeconomic factors/covariates impacts on mortality.Unadjusted 5 Table 4. Sex and Socioeconomic impacts on all-cause mortality.Adjusted  6

Municipalities
Sweden has a total population of just over 10 million inhabitants and is divided into three main parts: northern (Norrland, 11•4%), middle (Svealand, 40•8%), and southern Sweden (Gotaland, 47•8%).In 2021 there were 290 municipalities each with local differences in median income.The Gini coefficient, which ranges from 0-1, indicates income inequality within each municipality, with a higher value signifying greater inequality. 1 Municipalities vary between 2395 and 978770 inhabitants and southern Sweden is much more densely populated than the northern part of the country.

Health-care system
There are 21 healthcare regions, each with an average of 500 000 inhabitants.The healthcare regions have great autonomy and are responsible for the healthcare organisation within a framework set by the state.There are seven university hospitals, 23 regional hospitals, and 38 general hospitals.All hospitals provide an emergency service, but special healthcare services are restricted to the first two hospital categories only.Healthcare in Sweden is financed by taxes (85%) and patient fees (14%), and only 1% is covered by a voluntary health insurance scheme.Dental care is free up to 23 years of age and then partly covered by public health care. 2 All healthcare regions contribute to several national healthcare quality registers, aiming to develop and ensure the quality of care, produce data for statistics and research, and make it possible to compare and improve healthcare at national and regional levels.These registers contain sensitive information, but Sweden has rigorous data privacy regulations to protect the individual's integrity.Access to register data is strictly controlled and granted for research purposes after ethical and legal considerations.The National Board of Health and Welfare has a register containing a wide range of healthcare-related data, including diagnoses, treatments, prescriptions, hospital admissions, births and deaths, and cancer (the Cancer Register that, since 1958, has comprehensive data on all forms of cancer).These registers cover the entire of Sweden, providing a complete and accurate representation of its population's health with standard coding and reporting practices.Consequently, these registers are reliable sources of data for research and statistics.

Flowchart of the study population. Figure2. Swedish National registers used in this study and their timeframe. 2Table 1 . Swedish National Quality registers used to obtain information data on cancer patients and their controls.
1.Hasell J. Measuring inequality: What is the Gini coefficient?https://ourworldindata.org/what-is-the-gini-coefficient2023 2.National Board of Health and Welfare.Statistics and Data 2023 [Available from: https://www.socialstyrelsen.se/en/statistics-and-data/.Figure 1.

Time, age, sex and socioeconomic factors and covariates and all-cause mortality (univariable) for the 11 684 CAYAs and 8018 Controls who died.
Number of CAYAs and Controls in each demographic and socioeconomic analysis are listed in Figure6.Abbreviations: SEK= Swedish crowns.no=numbers.CAYA= child, adolescent, and young adult.km=kilometres.HR= hazard ratio.CI=confidence interval.